Addressing Hepatotoxicity in Clinical Practice for IDH-Mutant Gliomas

EP: 1.Redefining Gliomas Through Molecular Classification

EP: 2.Treatment Workflow for IDH-Mutant Gliomas

EP: 3.Integrating Molecular Markers Into Glioma Treatment Planning

EP: 4.Postsurgical Assessment and Early Management Considerations for IDH-Mutant Gliomas

EP: 5.Inside INDIGO: Updated Trial Insights and Clinical Implications

EP: 6.Beyond the Trial: Treatment Considerations and Sequencing for IDH-Mutant Gliomas

EP: 7.Monitoring and Managing Adverse Events With IDH Inhibitors

EP: 8.Recent Research and Future Directions in IDH-Mutant Gliomas

EP: 9.Case-Based Approach to Initial Treatment Planning for IDH-Mutant Gliomas

EP: 10.Treatment Options and Patient Counseling at Disease Progression in IDH-Mutant Gliomas

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EP: 11.Addressing Hepatotoxicity in Clinical Practice for IDH-Mutant Gliomas

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The second case presents a 45-year-old teacher with an IDH-mutant astrocytoma who developed progressive FLAIR signal changes 18 months after initial resection and was started on voracidinib. After 6 months of treatment, the patient developed ALT and AST elevations approximately 3 times the upper limit of normal, representing a borderline grade 1-2 toxicity. This scenario illustrates the common clinical challenge of managing mild hepatotoxicity in patients who are benefiting from IDH inhibitor therapy.

The expert panel recommends a cautious approach, suggesting temporary drug discontinuation with weekly monitoring until liver enzymes return to grade 1 or baseline levels. Given the relatively aggressive disease progression in this case (significant regrowth within 18 months), the oncologists emphasize avoiding dose reductions, when possible, to maintain therapeutic benefit. They note that this patient's significant disease burden and bilateral involvement necessitate maximizing the therapeutic dose of voracidinib for optimal disease control.

The experts emphasize the importance of balancing mild hepatotoxicity against clear evidence of disease progression and treatment response. Clinical experience suggests that many patients experience transient liver enzyme elevations that spontaneously resolve over several months, even while continuing therapy. The panel stresses investigating other potential causes of hepatotoxicity, including concurrent medications, supplements, and lifestyle factors such as alcohol and acetaminophen use. This comprehensive approach helps distinguish drug-related hepatotoxicity from other causes, enabling more informed treatment decisions and potentially avoiding unnecessary treatment discontinuation.